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Abstract

Directed cell migration is essential for wound healing, development and tissue morphogenesis. In vivo, geometrical cues from the extra-cellular matrix (ECM) are critical for the regulation of directed migration. During contact guidance, the fibrillar architecture of the ECM helps control cell shape and migration direction. Micropatterning has been a powerful tool to demonstrate that cells respond to the geometrical presentation of ligands, however mechanistic understanding of how cells sense changes in ECM geometry has been lacking. Here, we use micropatterning to systematically vary a single spatial dimension in ECM geometry and show that micron scale changes are sufficient to induce contact guidance. By manipulating the regulation of protrusive activity using different cellular mechanisms we show that contact guidance relies on spatial control of protrusive activity to direct migration. Specifically, we prove that area and orientation are the two physical parameters of protrusion that determine the ability of cells to undergo contact guidance. Contact guidance requires cells to translate subcellular changes in ECM geometry into cellular scale behaviors. To sculpt tissues, cell migration can be used to integrate changes at the cellular level and translate them into tissue scale behaviors. An example of such a process is the tissue level patterning in Drosophila egg chambers. During egg chamber elongation, the follicular epithelium undergoes collective migration causing the egg chamber to rotate within its surrounding ECM. Rotation coincides with the formation of a parallel array of actin bundles in the epithelium and fibrils in the ECM. By studying the cellular mechanisms of migration in egg chambers, we show that rotation plays a critical role in building the actin tissue-scale pattern. Rotation begins shortly after egg chamber formation and requires lamellipodial protrusions at each follicle cells leading edge. During early stages, rotation is necessary for tissue-level actin bundle alignment, but it becomes dispensable after the ECM is polarized. This work highlights how cell migration can be used to build a polarized tissue scale organization.

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